Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Antimelanogenic effect of ginsenoside Rg3 through extracellular signal-regulated kinase-mediated inhibition of microphthalmia-associated transcription factor

  • Lee, Seung Jae (CleanUp Dermatologic Clinic) ;
  • Lee, Woo Jin (Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Chang, Sung Eun (Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Ga-Young (Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine)
  • Received : 2014.10.05
  • Accepted : 2015.01.08
  • Published : 2015.07.15
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Abstract

Background: Panax ginseng has been used to prolong longevity and is believed to be useful for improving skin complexion. Ginsenosides are the most active components isolated from ginseng, and ginsenoside Rg3 (G-Rg3) in particular has been demonstrated to possess antioxidative, antitumorigenic, and anti-inflammatory properties. The aim of this study was to examine the ability of G-Rg3 to inhibit melanogenesis. Methods: The effects of G-Rg3 on melanin contents and the protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein 1 (TRP1) were evaluated. Melanogenesis-regulating signaling molecules such as Akt and extracellular signal-regulated kinase (ERK) were also examined to explore G-Rg3-induced antimelanogenic mechanisms. Results: G-Rg3 was found to significantly inhibit the synthesis of melanin in normal human epidermal melanocytes and B16F10 cells in a dose-dependent manner. The activity of cellular tyrosinase and the expression of MITF, tyrosinase, and TRP1 were all reduced, whereas ERK was strongly activated. PD98059 (a specific inhibitor of ERK) attenuated the G-Rg3-induced inhibition of melanin synthesis and tyrosinase activity. Conclusion: Taken together, these results showed that G-Rg3 induces the activation of ERK, which accounts for its antimelanogenic effects. G-Rg3 may be a promising safe skin-whitening agent, adding to the long list of uses of P. ginseng for the enhancement of skin beauty.

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References

  1. Briganti S, Camera E, Picardo M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003;16:101-10. https://doi.org/10.1034/j.1600-0749.2003.00029.x
  2. Böhm M, Luger TA. Alpha-melanocyte-stimulating hormone. Its current significance for dermatology. Hautarzt 2004;55:436-45 [Article in German]. https://doi.org/10.1007/s00105-004-0729-0
  3. Yamaguchi Y, Hearing VJ. Physiological factors that regulate skin pigmentation. Biofactors 2009;35:193-9. https://doi.org/10.1002/biof.29
  4. Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 2004;84:1155-228. https://doi.org/10.1152/physrev.00044.2003
  5. Kim DS, Hwang ES, Lee JE, Kim SY, Kwon SB, Park KC. Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation. J Cell Sci 2003;116:1699-706. https://doi.org/10.1242/jcs.00366
  6. Weber DA, Wheat JM, Currie GM. Cancer stem cells and the impact of Chinese herbs, isolates and other complementary medical botanicals: a review. Zhong Xi Yi Jie He Xue Bao 2012;10:493-503. https://doi.org/10.3736/jcim20120503
  7. Wei X, Chen J, Su F, Su X, Hu T, Hu S. Stereospecificity of ginsenoside Rg3 in promotion of the immune response to ovalbumin in mice. Int Immunol 2012;24:465-71. https://doi.org/10.1093/intimm/dxs043
  8. Joo SS, Yoo YM, Ahn BW, Nam SY, Kim YB, Hwang KW. Lee do I. Prevention of inflammation-mediated neurotoxicity by Rg3 and its role in microglial activation. Biol Pharm Bull 2008;31:1392-6. https://doi.org/10.1248/bpb.31.1392
  9. Rivera E, Daggfeldt A, Hu S. Ginseng extract in aluminium hydroxide adjuvanted vaccines improves the antibody response of pigs to porcine parvovirus and Erysipelothrix rhusiopathiae. Vet Immunol Immunopathol 2003;91:19-27. https://doi.org/10.1016/S0165-2427(02)00269-6
  10. Rivera E, Hu S, Concha C. Ginseng and aluminium hydroxide act synergistically as vaccine adjuvants. Vaccine 2003;21:1149-57. https://doi.org/10.1016/S0264-410X(02)00518-2
  11. Hu S, Concha C, Lin F, Persson Waller K. Adjuvant effect of ginseng extracts on the immune responses to immunization against Staphylococcus aureus in dairy cattle. Vet Immunol Immunopathol 2003;91:29-37. https://doi.org/10.1016/S0165-2427(02)00264-7
  12. Hu YL, Kong XF, Rui R, Wang D, Li X. Effects of Chinese herbal medicinal ingredients on peripheral lymphocyte proliferation and serum antibody titer after vaccination in chicken. Int Immunopharmacol 2004;4:975-82. https://doi.org/10.1016/j.intimp.2004.03.008
  13. Rivera E, Ekholm Pettersson F, Inganäs M, Paulie S, Grönvik KO. The Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune response. Vaccine 2005;23:5411-9. https://doi.org/10.1016/j.vaccine.2005.04.007
  14. So MW, Lee EJ, Lee HS, Koo BS, Kim YG, Lee CK, Yoo B. Protective effects of ginsenoside Rg3 on human osteoarthritic chondrocytes. Mod Rheumatol 2013;23:104-11. https://doi.org/10.3109/s10165-012-0635-8
  15. Wei X, Su F, Su X, Hu T, Hu S. Stereospecific antioxidant effects of ginsenoside Rg3 on oxidative stress induced by cyclophosphamide in mice. Fitoterapia 2012;83:636-42. https://doi.org/10.1016/j.fitote.2012.01.006
  16. Tu CX, Lin M, Lu SS, Qi XY, Zhang RX, Zhang YY. Curcumin inhibits melanogenesis in human melanocytes. Phytother Res 2012;26:174-9. https://doi.org/10.1002/ptr.3517
  17. Jang JY, Lee JH, Kang BW, Chung KT, Choi YH, Choi BT. Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells. Exp Dermatol 2009;18:232-7. https://doi.org/10.1111/j.1600-0625.2008.00794.x
  18. Wu LC, Lin YY, Yang SY, Weng YT, Tsai YT. Antimelanogenic effect of cphycocyanin through modulation of tyrosinase expression by upregulation of ERK and downregulation of p38 MAPK signaling pathways. J Biomed Sci 2011;18:74. https://doi.org/10.1186/1423-0127-18-74
  19. Jang JY, Lee JH, Jeong SY, Chung KT, Choi YH, Choi BT. Partially purified Curcuma longa inhibits alpha-melanocyte-stimulating hormone-stimulated melanogenesis through extracellular signal-regulated kinase or Akt activation-mediated signalling in B16F10 cells. Exp Dermatol 2009;18: 689-94. https://doi.org/10.1111/j.1600-0625.2009.00857.x
  20. Kim DS, Lee HK, Park SH, Chae CH, Park KC. AVS-1357 inhibits melanogenesis via prolonged ERK activation. Pharmazie 2009;64:532-7.
  21. Olivares C, Solano F. New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins. Pigment Cell Melanoma Res 2009;22:750-60. https://doi.org/10.1111/j.1755-148X.2009.00636.x
  22. Engasser PE, Maibach HI. Cosmetics and dermatology: bleaching creams. J Am Acad Dermatol 1981;5:143-7. https://doi.org/10.1016/S0190-9622(81)70082-3
  23. Kim YS, Kim DS, Kim SI. Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells I into granulocytes: modulation of protein kinase C isoforms during differentiation by ginsenoside Rh2. Int J Biochem Cell Biol 1998;30: 327-38. https://doi.org/10.1016/S1357-2725(97)00141-6
  24. Liu ZQ. Chemical insights into ginseng as a resource for natural antioxidants. Chem Rev 2012;112:3329-55. https://doi.org/10.1021/cr100174k
  25. Lee TF, Shiao YJ, Chen CF, Wang LC. Effect of ginseng saponins on betaamyloid- suppressed acetylcholine release from rat hippocampal slices. Planta Med 2001;67:634-7. https://doi.org/10.1055/s-2001-17366
  26. Lu JM, Yao Q, Chen C. Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol 2009;7:293-302. https://doi.org/10.2174/157016109788340767
  27. Chou TH, Ding HY, Hung WJ, Liang CH. Antioxidative characteristics and inhibition of alpha-melanocyte-stimulating hormone-stimulated melanogenesis of vanillin and vanillic acid from Origanum vulgare. Exp Dermatol 2010;19:742-50.
  28. Kang KS, Yokozawa T, Yamabe N, Kim HY, Park JH. ESR study on the structure and hydroxyl radical-scavenging activity relationships of ginsenosides isolated from Panax ginseng C A Meyer. Biol Pharm Bull 2007;30:917-21. https://doi.org/10.1248/bpb.30.917
  29. Kang KS, Kim HY, Baek SH, Yoo HH, Park JH, Yokozawa T. Study on the hydroxyl radical scavenging activity changes of ginseng and ginsenoside-Rb2 by heat processing. Biol Pharm Bull 2007;30:724-8. https://doi.org/10.1248/bpb.30.724
  30. Kang KS, Yamabe N, Kim HY, Okamoto T, Sei Y, Yokozawa T. Increase in the free radical scavenging activities of American ginseng by heat processing and its safety evaluation. J Ethnopharmacol 2007;113:225-32. https://doi.org/10.1016/j.jep.2007.05.027
  31. Kim DS, Kim SY, Chung JH, Kim KH, Eun HC, Park KC. Delayed ERK activation by ceramide reduces melanin synthesis in human melanocytes. Cell Signal 2002;14:779-85. https://doi.org/10.1016/S0898-6568(02)00024-4

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